We propose to define the effect of acute and chronic alcohol consumption on human and animal host defense mechanisms. We have evaluated granulocyte, cell-mediated immune, and humoral components of host defense during acute intoxication, chronic drinking in a controlled environment, and in alcoholics drinking in an uncontrolled situation, "on the street." We have found that the major defect in granulocyte function is in its ability to adhere to surfaces, and that poor adherence correlates with poor delivery of granulocytes to areas of inflammation. Furthermore, correction of the adherence defect will correct the cell delivery defect as well. Defects in chemotaxis have been noted in chronic ingestion, and the ability to respond to a new antigenic challenge with either cell-mediated immunity or antibody formation is impaired. We plan to pursue these findings as follows: a. The kinetic effect of acute intoxication on mobilization of granulocytes from the bone marrow will be assessed by administration of glucocorticoids or endotoxin to intoxicated rabbits and following their counts. b. Adherence defects secondary to glucocorticoid therapy will be studied, to determine whether they can be reversed pharmacologically, thereby improving granulocyte delivery. If so, the adherence defect induced by intoxication can be seen as part of a general attribute of anti-inflammatory drugs. o